This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stroke is the third leading cause of death in the U.S. and the leading cause of disability. More women than men die from stroke, although men have a higher incidence of stroke. There many other gender differences that are becoming recognized as important, as well, such as risk profiles. For example, men with stroke are more likely to have coronary disease, peripheral vascular disease, and tobacco smoking, whereas, women are more likely to have atrial fibrillation and hypertension. Women also have acceleration of risk factors associated with menopause, which is believed to be related to endogenous estrogen depletion. During this time women frequently develop increased blood pressure and fasting glucose, an atherogenic lipid profile, weight gain, and progression of subclinical atherosclerosis in the carotid arteries. Therefore, in women, mid-life changes may significantly accelerate stroke risk, but many of these changes may be unrecognized because they are subclinical. In addition, various measures of subclinical vascular disease may differ depending on the presence of specific risk factors. Therefore, if only one vascular measure is performed, it may not adequately represent the impact of specific risk factors, and these effects may be sex-specific. In addition, prevention strategies are increasingly being studied with intermediate measures of vascular disease. Investigations of midlife subclinical vascular disease in men and women would aid in our understanding of the risk factors, and biomarkers that impact subclinical risk. This could then lead to sex-specific strategies of prevention earlier than would otherwise occur without knowledge of subclinical disease.